Lacosamide

Identification

Name

Lacosamide

Accession Number

DB06218

Type

Small Molecule

Groups

Approved

Description

Lacosamide is a functionalized amino acid that has activity in the maximal electroshock seizure test, and is indicated for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain. Recent studies indicate that Lacosamide only affects those neurons which are depolarized or active for long periods of time, typical of neurons at the focus of an epileptic seizure, as opposed to other antiepileptic drugs such as carbamazepine or lamotrigine which slow the recovery from inactivation and reduce the ability of neurons to fire action potentials.

Lacosamide therapy is correlated with a decrease in seizure frequency. It should be noted that in group analyses, dosages above 400 mg/day do not appear to result in additional benefit.

Mechanism of action

It is proposed that lacosamide's inhibition of sodium channels is responsible for analgesia. Lacosamide may be selective for inhibiting depolarized neurons rather than neurons with normal resting potentials. Pain and nociceptor hyperexcitability are associated with neural membrane depolarization. Lacosamide binds to collapsin response mediator protein-2 (CRMP-2), a phosphoprotein which is expressed primarily in the nervous system and is involved in neuronal differentiation and control of axonal outgrowth. The role CRMP-2 of binding in seizure control is hasn't been elucidated.

Lacosamide has a negligible first pass effect with bioavailability of about 100%. The maximum Lacosamide plasma concentrations occur about 1-4 hours after oral administration, and the pharmacokinetics of Lacosamide are dose proportional. Food does not affect absorption.

Volume of distribution

approximately 0.6 L/kg; thus close to the volume of total body water.

Protein binding

<15%

Metabolism

Lacosamide is a CYP2C19 substrate. The relative contribution of other CYP isoforms or non-CYP enzymes in the metabolism of lacosamide is not known. Primary compounds excreted were unchanged lacosamide (approximately 40% of the dose), its O-desmethyl metabolite (approximately 30%), and a structurally unknown polar fraction (~20%). The plasma exposure of the major human metabolite, O-desmethyl-lacosamide, is approximately 10% of that of lacosamide. This metabolite has no known pharmacological activity.

Taxonomy

Description

This compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.